JP5346016B2 - Ｓ１ｐ１受容体アゴニストとしての新規ジカルボン酸誘導体 - Google Patents

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Publication number

JP5346016B2

JP5346016B2 JP2010511664A JP2010511664A JP5346016B2 JP 5346016 B2 JP5346016 B2 JP 5346016B2 JP 2010511664 A JP2010511664 A JP 2010511664A JP 2010511664 A JP2010511664 A JP 2010511664A JP 5346016 B2 JP5346016 B2 JP 5346016B2

Authority

JP

Japan

Prior art keywords

benzyl

piperidine

oxadiazol

dicarboxylic acid

fluoro

Prior art date

2007-06-15

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

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• 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 title claims abstract description 25
• 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 title abstract description 23
• 239000000018 receptor agonist Substances 0.000 title abstract description 8
• 229940044601 receptor agonist Drugs 0.000 title abstract description 8
• 150000001990 dicarboxylic acid derivatives Chemical class 0.000 title abstract description 4
• 238000000034 method Methods 0.000 claims abstract description 46
• 238000002360 preparation method Methods 0.000 claims abstract description 42
• 230000008569 process Effects 0.000 claims abstract description 8
• 150000001875 compounds Chemical class 0.000 claims description 126
• -1 4-isobutyrylphenyl Chemical group 0.000 claims description 106
• 239000000203 mixture Substances 0.000 claims description 77
• 150000003839 salts Chemical class 0.000 claims description 37
• 150000002148 esters Chemical class 0.000 claims description 35
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 34
• 229910052739 hydrogen Inorganic materials 0.000 claims description 33
• 239000001257 hydrogen Substances 0.000 claims description 32
• 125000003118 aryl group Chemical group 0.000 claims description 30
• 125000000217 alkyl group Chemical group 0.000 claims description 27
• 239000012453 solvate Substances 0.000 claims description 22
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
• 150000004677 hydrates Chemical class 0.000 claims description 19
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 18
• 125000004432 carbon atom Chemical group C* 0.000 claims description 18
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
• 229910052736 halogen Inorganic materials 0.000 claims description 17
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• CCQPAEQGAVNNIA-UHFFFAOYSA-L cyclobutane-1,1-dicarboxylate(2-) Chemical compound [O-]C(=O)C1(C([O-])=O)CCC1 CCQPAEQGAVNNIA-UHFFFAOYSA-L 0.000 claims description 4
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• CCQPAEQGAVNNIA-UHFFFAOYSA-N cyclobutane-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CCC1 CCQPAEQGAVNNIA-UHFFFAOYSA-N 0.000 claims description 3
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• QYQADNCHXSEGJT-UHFFFAOYSA-N cyclohexane-1,1-dicarboxylate;hydron Chemical compound OC(=O)C1(C(O)=O)CCCCC1 QYQADNCHXSEGJT-UHFFFAOYSA-N 0.000 claims description 2
• 206010012601 diabetes mellitus Diseases 0.000 claims description 2
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• ZVYNEIVHNNYCSE-UHFFFAOYSA-N piperidine-4,4-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CCNCC1 ZVYNEIVHNNYCSE-UHFFFAOYSA-N 0.000 claims description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
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• 150000002431 hydrogen Chemical group 0.000 claims 4
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• 208000000112 Myalgia Diseases 0.000 claims 1
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• 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
• 208000026278 immune system disease Diseases 0.000 claims 1
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• JJBDWBUEPCGFMN-UHFFFAOYSA-N 3-phenyl-1,2,4-oxadiazole Chemical group O1C=NC(C=2C=CC=CC=2)=N1 JJBDWBUEPCGFMN-UHFFFAOYSA-N 0.000 abstract 1
• SNFAEUZNFIYGNA-UHFFFAOYSA-N 5-phenyl-1,2,4-oxadiazole Chemical compound C1=NOC(C=2C=CC=CC=2)=N1 SNFAEUZNFIYGNA-UHFFFAOYSA-N 0.000 abstract 1
• 230000001225 therapeutic effect Effects 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 228
• 238000005481 NMR spectroscopy Methods 0.000 description 150
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
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• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 87
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 81
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 80
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• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
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